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EpCAM aptamer mediated cancer cell specific delivery of EpCAM siRNA using polymeric nanocomplex

Subramanian, Nithya, Kanwar, Jagat R., Athalya, Prasanna Kumar, Janakiraman, Narayanan, Khetan, Vikas, Kanwar, Rupinder K., Eluchuri, Sailaja and Krishnakumar, Subramanian 2015, EpCAM aptamer mediated cancer cell specific delivery of EpCAM siRNA using polymeric nanocomplex, Journal of biomedical science, vol. 22, no. 4, pp. 1-10, doi: 10.1186/s12929-014-0108-9.

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Title EpCAM aptamer mediated cancer cell specific delivery of EpCAM siRNA using polymeric nanocomplex
Author(s) Subramanian, Nithya
Kanwar, Jagat R.ORCID iD for Kanwar, Jagat R. orcid.org/0000-0003-3728-9568
Athalya, Prasanna Kumar
Janakiraman, Narayanan
Khetan, Vikas
Kanwar, Rupinder K.
Eluchuri, Sailaja
Krishnakumar, Subramanian
Journal name Journal of biomedical science
Volume number 22
Issue number 4
Start page 1
End page 10
Total pages 10
Publisher BioMed Central
Place of publication London, Eng.
Publication date 2015
ISSN 1423-0127
Keyword(s) Aptamer
Cancer targeting
EpCAM
PEI-EpApt-SiEp
siRNA delivery
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Medicine, Research & Experimental
Research & Experimental Medicine
TARGETED DRUG-DELIVERY
ADHESION MOLECULE APTAMER
IN-VITRO
NONVIRAL CARRIERS
GENE DELIVERY
NANOPARTICLES
POLYETHYLENIMINE
DNA
VIVO
RNA
Summary BACKGROUND: Epithelial cell adhesion molecule (EpCAM) is overexpressed in solid tumors and regarded as a putative cancer stem cell marker. Here, we report that employing EpCAM aptamer (EpApt) and EpCAM siRNA (SiEp) dual approach, for the targeted delivery of siRNA to EpCAM positive cancer cells, efficiently inhibits cancer cell proliferation. RESULTS: Targeted delivery of siRNA using polyethyleneimine is one of the efficient methods for gene delivery, and thus, we developed a novel aptamer-PEI-siRNA nanocomplex for EpCAM targeting. PEI nanocomplex synthesized with EpCAM aptamer (EpApt) and EpCAM siRNA (SiEp) showed 198 nm diameter sized particles by dynamic light scattering, spherical shaped particles, of 151 ± 11 nm size by TEM. The surface charge of the nanoparticles was -30.0 mV using zeta potential measurements. Gel retardation assay confirmed the PEI-EpApt-SiEp nanoparticles formation. The difference in size observed by DLS and TEM could be due to coating of aptamer and siRNA on PEI nanocore. Flow cytometry analysis revealed that PEI-EpApt-SiEp has superior binding to cancer cells compared to EpApt or scramble aptamer (ScrApt) or PEI-ScrApt-SiEp. PEI-EpApt-SiEp downregulated EpCAM and inhibited selectively the cell proliferation of MCF-7 and WERI-Rb1 cells. CONCLUSIONS: The PEI nanocomplex fabricated with EpApt and siEp was able to target EpCAM tumor cells, deliver the siRNA and silence the target gene. This nanocomplex exhibited decreased cell proliferation than the scrambled aptamer loaded nanocomplex in the EpCAM expressing cancer cells and may have potential for EpCAM targeting in vivo.
Language eng
DOI 10.1186/s12929-014-0108-9
Field of Research 111299 Oncology and Carcinogenesis not elsewhere classified
Socio Economic Objective 920102 Cancer and Related Disorders
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2015, BioMed Central
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30075687

Document type: Journal Article
Collections: School of Medicine
Open Access Collection
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Created: Tue, 18 Aug 2015, 15:25:05 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.